Coronaviruses and parainfluenza viruses represent two important viral etiologies of severe lower respiratory infections in human populations. While the emergence of SARS-CoV-2 in 2019 has led to the development of effective vaccines, interventions to prevent or treat coronaviruses remain limited. There are currently no approved vaccines or therapeutics to combat parainfluenza viruses. Coronaviruses and parainfluenza viruses are enveloped RNA viruses that enter host cells through fusion of the viral and cellular membranes, carried out by fusion proteins expressed on the virion surface. The coronaviruse spike (S) and parainfluenza virus fusion protein (F) are class I fusion proteins, which form metastable, prefusion homotrimers that irreversibly transition to a stable postfusion conformation to facillitate membrane fusion. Due to their critical role in cellular entry, class I fusion proteins are a major target of neutralizing antibodies, which are critical for a protective immune response to infection or vaccination and can be developed into antiviral therapies. The first section of this dissertation describes the development of a highly stable SARS-CoV-2 spike vaccine antigen (HexaPro) and the discovery and characterization of several spike-directed antibodies. A subset of these antibodies neutralize SARS-CoV-2 infection by blocking binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). We found one non-neutralizing antibody, 54043-5, capable of binding multiple coronaviruses within the same genus. The structure of 54043-5 bound the SARS-CoV-2 spike fusion machinery revealed a highly conserved, cryptic epitope at the apex of the spike fusion machinery that may be exploited through antibody engineering to provide protection from disease. The second section of this dissertation describes the development of a prefusion-stabilized F antigen (OnlyEcto) from human respiroviurs 3 (RV3), the most commonly detected parainfluenza virus serotype. We report that OnlyEcto elicits a robust neutralizing antibody response when used to immunize mice. Structural studies were also conducted to investigate the neutralization mechanims of three RV3 F-directed camelid nanobodies. Collectively, these studies provide important molecular details about the antigenicity of the SARS-CoV-2 spike and RV3 F proteins that support the development of safe and effective interventions to combat these two important viruses.